Disease-associated cerebrospinal fluid (CSF) protein changes that were previously identified by this group have been further investigated: The presence of two 30,000 MW proteins in CSF of Creutzfeldt-Jakob disease (CJD) patients have been studied prospectively for their usefulness in the diagnosis of 70 nationally and internationally referred cases: no false positives or false negatives were found in the 30 cases that have so far come to autopsy (this has included 3 cases of in-vivo diagnosis of growth hormone transmitted CJD). Further characterization of abnormal CSF proteins have led to purification of 8 proteins for structural analysis, and one of these, a glycoprotein, has been partially sequenced. Four peptide fragments, obtained from a tryptic acid digest, 8 to 18 amino acids in length have been sequenced from this protein. These sequences represent a new protein that has not previously been characterized in the protein sequence data banks. This glycoprotein has been shown to be quantitatively altered in schizophrenia, Parkinson's Disease and multiple sclerosis. Two dimensional electrophoretic survey studies of brain have been initiated with inbred strains of mice, with a view to developing a protein reference map for both genetic murine disorders and human brain disorders. Similar studies have led to the observation of protein alternations in learning mutants of Drosophila, and T lymphocytes infected with the human immunodeficiency virus. Continued efforts to investigate protein detection methods has permitted us to develop a physical explanation for the production of specific colors by protein stained with certain silver stains. Electron microscopic studies coupled with computerized image analysis provided evidence that the colors are formed by light scattering which is caused by the presence of silver grains of specific sizes in the gel. Silver grains in yellow bands had an average size of 29.6nm while those in blue bands were 71.6nm in diameter.